感染羊瘙痒因子263K株或139A株仓鼠脑组织中tau蛋白和磷酸化tau蛋白变化的研究  

Alternations of Tau Protein and Its Phosphorylated Profiles in the Experimental Hamsters Infected by Scrapie Agents 263K and 139A

作　　者：王桂荣[1] 石崧[1] 高晨[1] 张宝云[1] 田婵[1] 董辰方[1] 周瑞敏[1] 李晓丽[1] 陈操[1] 韩俊[1] 董小平[1] 

机构地区：[1]中国疾病预防控制中心病毒病预防控制所传染病预防控制国家重点实验室,北京100052

出　　处：《病毒学报》2009年第3期202-207,共6页Chinese Journal of Virology

基　　金：国家科技攻关项目(2006BAD06A13-2);国家973项目(2007CB310505);国家自然科学基金委项目(No.30500018;30571672)资助

摘　　要：为探讨朊病毒病的神经病理特征,应用Western blot方法检测了感染羊瘙痒因子263K株或139A株的仓鼠脑组织中总tau蛋白和Ser396和Ser404位点发生磷酸化tau蛋白表达水平的变化;并应用Real Time PCR方法检测了tau mRNAs转录活性的改变。结果表明总tau蛋白含量升高而Ser396和Ser404位点发生磷酸化的tau蛋白含量降低,该现象与羊瘙痒因子毒株类型和临床潜伏期无关;感染羊瘙痒因子的仓鼠脑组织中Tau2和Tau4这两个异构体的转录水平升高。这些结果表明tau蛋白在Ser396和Ser404位点的去磷酸化可能与朊病毒病发病相关。In human prion diseases, phosphorylated-tau deposition has been described in a rare genetic form, Gerstmann-Straussler-Scheinker disease, but is not considered part of the neuropathological picture of Creutzfeldt-Jakob disease. To investigate the possible changes of tau and phosphorylated tau （Ser396/ Ser404） in transmissible spongiform encephalopathies （TSEs）, the expressions and transcriptions of above biological factors in the brain tissues of 263K- and 139A-infected hamsters were evaluated by Western blots and Real Time PCR, respectively, followed by quantitative analyses of immunoblot images and relative transcriptional levels compared with normal animals. The contents of total tau increased, but phosphorylated tau at Ser396 and Ser404 decreased, regardless of the types of scrapie agents and clinical incubations. Transcriptions of two tau isoforms were also markedly increased. These findings suggested that dephosphorylation of tau at Ser396/Ser404 was a illness-correlative phenomenon in TSEs. Alterations of tau and phosphorylated tau （Ser396/Ser404） were either intermediate or consequent events in TSE pathogenesis and proposed the potential linkage of these bioactive proteins with the pathogenesis of prion diseases.

关 键 词：朊病毒 羊瘙痒因子 TAU蛋白 磷酸化TAU蛋白 

分 类 号：R373.9[医药卫生—病原生物学]